tbuckley/cabot-search huggingface dataset:
Taking Steps to Promote Diversity, Equity, and Inclusion in the Surgical Workforce
Authors: Steven W. Thornton, Harold J. Leraas, Elisabeth T. Tracy
Journal: JAMA Surgery (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Noninvasive interrogation of CD8+ T cell effector function for monitoring early tumor responses to immunotherapy
Authors: Haoyi Zhou, Yanpu Wang, Hongchuang Xu, Xiuling Shen, Ting Zhang, Xin Zhou, Yuwen Zeng, Kui Li, Li Zhang, Hua Zhu, Xing Yang, Nan Li, Zhi Yang, Zhaofei Liu
Journal: Journal of Clinical Investigation (2022)

Accurately identifying patients who respond to immunotherapy remains clinically challenging. A noninvasive method that can longitudinally capture information about immune cell function and assist in the early assessment of tumor responses is highly desirable for precision immunotherapy. Here, we show that PET imaging using a granzyme B–targeted radiotracer named 68Ga-grazytracer, could noninvasively and effectively predict tumor responses to immune checkpoint inhibitors and adoptive T cell transfer therapy in multiple tumor models. 68Ga-grazytracer was designed and selected from several radiotracers based on non-aldehyde peptidomimetics, and exhibited excellent in vivo metabolic stability and favorable targeting efficiency to granzyme B secreted by effector CD8+ T cells during immune responses. 68Ga-grazytracer permitted more sensitive discrimination of responders and nonresponders than did 18F-fluorodeoxyglucose, distinguishing between tumor pseudoprogression and true progression upon immune checkpoint blockade therapy in mouse models with varying immunogenicity. In a preliminary clinical trial with 5 patients, no adverse events were observed after 68Ga-grazytracer injection, and clinical responses in cancer patients undergoing immunotherapy were favorably correlated with 68Ga-grazytracer PET results. These results highlight the potential of 68Ga-grazytracer PET to enhance the clinical effectiveness of granzyme B secretion–related immunotherapies by supporting early response assessment and precise patient stratification in a noninvasive and longitudinal manner.
Variation in Population Attributable Fraction of Dementia Associated With Potentially Modifiable Risk Factors by Race and Ethnicity in the US
Authors: Mark Lee, Eric Whitsel, Christy Avery, Timothy M. Hughes, Michael E. Griswold, Sanaz Sedaghat, Rebecca F. Gottesman, Thomas H. Mosley, Gerardo Heiss, Pamela L. Lutsey
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Identifying modifiable risk factors that are associated with dementia burden across racial and ethnic groups in the population can yield insights into the potential effectiveness of interventions in preventing dementia and reducing disparities. <h3>Objective</h3> To calculate the population attributable fraction (PAF) of dementia associated with 12 established modifiable risk factors for all US adults, as well as separately by race and ethnicity. <h3>Design, Setting, and Participants</h3> This cross-sectional study used survey data from nationally representative samples of US adults. PAFs were calculated using relative risks and prevalence estimates for 12 risk factors. Relative risks were taken from meta-analyses, as reported in a 2020 systematic review. Prevalence estimates for risk factors were derived from nationally representative cross-sectional survey data collected between 2011 and 2018. Combined PAFs were adjusted for risk factor communality using weights derived from the Atherosclerosis Risk in Communities (ARIC) study (1987-2018). Analyses were conducted May through October 2021. <h3>Exposures</h3> Low education, hearing loss, traumatic brain injury, hypertension, excessive alcohol consumption, obesity, smoking, depression, social isolation, physical inactivity, diabetes, and air pollution. <h3>Main Outcomes and Measures</h3> PAF for each dementia risk factor, a combined PAF, and the decrease in the number of prevalent dementia cases in 2020 that would be expected given a 15% proportional decrease in each exposure. <h3>Results</h3> Among all US adults, an estimated 41.0% (95% CI, 22.7%-55.9%) of dementia cases were attributable to 12 risk factors. A 15% proportional decrease in each risk factor would reduce dementia prevalence in the population by an estimated 7.3% (95% CI, 3.7%-10.9%). The estimated PAF was greater for Black and Hispanic than it was for White and Asian individuals. The greatest attributable fraction of dementia cases was observed for hypertension (PAF, 20.2%; 95% CI, 6.3%-34.4%), obesity (PAF, 20.9%; 95% CI, 13.0%-28.8%), and physical inactivity (PAF, 20.1%; 95% CI, 9.1%-29.6%). These factors were also highest within each racial and ethnic group, although the proportions varied. <h3>Conclusions and Relevance</h3> A large fraction of dementia cases in the US were associated with potentially modifiable risk factors, especially for Black and Hispanic individuals. Targeting and reducing these risk factors may curb the projected rise in dementia cases over the next several decades.
Associations Between Pregnancy-Related Predisposing Factors for Offspring Neurodevelopmental Conditions and Parental Genetic Liability to Attention-Deficit/Hyperactivity Disorder, Autism, and Schizophrenia
Authors: Alexandra Havdahl, Robyn E. Wootton, Beate Leppert, Lucy Riglin, Helga Ask, Martin Tesli, Ragna Bugge Askeland, Laurie J. Hannigan, Elizabeth Corfield, Anne-Siri Øyen, Ole A. Andreassen, Kate Tilling, George Davey Smith, Anita Thapar, Ted Reichborn-Kjennerud, Evie Stergiakouli
Journal: JAMA Psychiatry (2022)

Several maternal exposures during pregnancy are considered predisposing factors for offspring neurodevelopmental conditions. However, many of these exposures may be noncausal and biased by maternal genetic liability.
Lipid nanoparticles to silence androgen receptor variants for prostate cancer therapy
Authors: Joslyn Quick, Nancy Dos Santos, Miffy H.Y. Cheng, Nisha Chander, Cedric A. Brimacombe, Jayesh Kulkarni, Roy van der Meel, Yuen Yi C. Tam, Dominik Witzigmann, Pieter R. Cullis
Journal: Journal of Controlled Release (2022)
A GPI-anchored Neurexin 3 proteoform mediates dendritic inhibition
Authors: Shinichiro Oku, Tabrez J. Siddiqui
Journal: Neuron (2022)

Neuronal wiring is facilitated by diverse synaptic adhesion proteins and their repertoire of alternatively spliced isoforms. In this issue of Neuron, Hauser et al. (2022) uncovered the role of a GPI-anchored neurexin 3 splice variant in inhibitory synapse development and dendritic inhibition.
Double-clip traction endoscopic submucosal dissection: an interesting alternative method for the resection of pedunculated polyps
Authors: Jérémie Albouys, Sophie Geyl, Lambin Thomas, Thibault Kaighobadi, Romain Legros, Mathieu Pioche, Jérémie Jacques
Journal: Endoscopy (2022)

The management of pedunculated polyps can be challenging due to the bleeding risk and the technical difficulty in positioning the snare. In cases of a head diameter > 20 mm and/or stalk width > 10 mm, prevention of bleeding is necessary by injection of diluted adrenalin and/or mechanical hemostatic prevention, as recommended by the European Society of Gastrointestinal Endoscopy [1]. Mechanical prevention can hamper resection by causing difficulties in snare opening and placement. In addition to size, the nature of the polyp also influences the bleeding risk, and hamartomatous/juvenile polyps have a higher propensity to bleed [2].
Epithelial HNF4A shapes the intraepithelial lymphocyte compartment via direct regulation of immune signaling molecules
Authors: Xuqiu Lei, Natalia Ketelut-Carneiro, Liraz Shmuel-Galia, Weili Xu, Ruth Wilson, Tim Vierbuchen, Yongzhi Chen, Andrea Reboldi, Joonsoo Kang, Karen L. Edelblum, Doyle Ward, Katherine A. Fitzgerald
Journal: The Journal of Experimental Medicine (2022)

Hepatocyte nuclear factor 4 α (HNF4A) is a highly conserved nuclear receptor that has been associated with ulcerative colitis. In mice, HNF4A is indispensable for the maintenance of intestinal homeostasis, yet the underlying mechanisms are poorly characterized. Here, we demonstrate that the expression of HNF4A in intestinal epithelial cells (IECs) is required for the proper development and composition of the intraepithelial lymphocyte (IEL) compartment. HNF4A directly regulates expression of immune signaling molecules including butyrophilin-like (Btnl) 1, Btnl6, H2-T3, and Clec2e that control IEC-IEL crosstalk. HNF4A selectively enhances the expansion of natural IELs that are TCRγδ+ or TCRαβ+CD8αα+ to shape the composition of IEL compartment. In the small intestine, HNF4A cooperates with its paralog HNF4G, to drive expression of immune signaling molecules. Moreover, the HNF4A-BTNL regulatory axis is conserved in human IECs. Collectively, these findings underscore the importance of HNF4A as a conserved transcription factor controlling IEC-IEL crosstalk and suggest that HNF4A maintains intestinal homeostasis through regulation of the IEL compartment.
Balovaptan vs Placebo for Social Communication in Childhood Autism Spectrum Disorder
Authors: Eric Hollander, Suma Jacob, Roger Jou, Nora McNamara, Linmarie Sikich, Russell Tobe, Janice Smith, Kevin Sanders, Lisa Squassante, Lorraine Murtagh, Teresa Gleissl, Christoph Wandel, Jeremy Veenstra-VanderWeele
Journal: JAMA Psychiatry (2022)

There are no approved medications for the core symptoms of autism spectrum disorder (ASD), socialization and communication difficulties.To evaluate the efficacy and safety of balovaptan, an oral selective vasopressin 1a receptor antagonist, compared with placebo in children and adolescents with ASD.The aV1ation study was a randomized, double-blind, 24-week, parallel-group, placebo-controlled phase 2 trial. Between November 22, 2016, and September 3, 2019, individuals were screened and randomly assigned to treatment groups. The primary efficacy analysis population comprised participants taking age-adjusted balovaptan equivalent to a 10-mg adult dose and participants from the concurrently randomized placebo group. This multicenter trial took place across 41 sites in the US. Participants were aged 5 to 17 years with diagnosed ASD and an IQ of 70 or greater. Data were analyzed from April 8 to November 16, 2020.Participants were randomly assigned to daily 4-mg or 10-mg adult-equivalent balovaptan or placebo, until the 4-mg group was discontinued.The primary end point was change from baseline on the Vineland-II two-domain composite (2DC; socialization and communication domains) score at week 24.Between November 2016 and September 2019, a total of 599 individuals were screened and 339 participants were randomly assigned to receive 4-mg balovaptan adult-equivalent dose (91 [26.8%]), 10-mg balovaptan adult-equivalent dose (126 [37.2%]), or placebo (122 [36.0%]). Primary analysis included 86 participants assigned to receive 10-mg balovaptan adult-equivalent dose and 81 assigned to receive placebo (mean [SD] age, 12.1 [3.4] years; 139 male participants [83.2%]). No statistically significant differences were observed between the balovaptan and placebo groups in change from baseline on the Vineland-II 2DC score at week 24 (difference in adjusted least-squares mean, -0.16; 90% CI, -2.56 to 2.23; P = .91). No improvements for balovaptan vs placebo were observed at week 24 for any secondary end points. Balovaptan was well tolerated with no emerging safety concerns. Similar proportions of participants reported adverse events (balovaptan, 66 of 86 [76.7%] vs placebo, 61 of 81 [75.3%]) and serious adverse events (balovaptan, 1 of 86 [1.2%] vs placebo, 4 of 81 [4.9%]).In this randomized clinical trial, balovaptan did not demonstrate efficacy in improvement of socialization and communication in this population with pediatric ASD. Balovaptan was well tolerated in children 5 years or older. Further development of robust, sensitive, and objective outcome measures may help to improve future studies in the assessment of therapies targeting communication and socialization in pediatric ASD.ClinicalTrials.gov Identifier: NCT02901431.
Age and the relative importance of liver‐related deaths in nonalcoholic fatty liver disease
Authors: Huapeng Lin, Terry Cheuk‐Fung Yip, Xinrong Zhang, Guanlin Li, Yee‐Kit Tse, Vicki Wing‐Ki Hui, Lilian Yan Liang, Jimmy Che‐To Lai, Stephen Lam Chan, Henry Lik‐Yuen Chan, Grace Lai‐Hung Wong, Vincent Wai‐Sun Wong
Journal: Hepatology (2022)

Background and Aims: It is unclear if the leading causes of death in patients with NAFLD differ by age. We aimed to investigate if the relative importance of liver‐related deaths is lower and overshadowed by cardiovascular and cancer‐related deaths in the elderly population. Approach and Results: We conducted a territory‐wide retrospective cohort study of adult patients with NAFLD between 2000 and 2021 in Hong Kong. The outcomes of interest were all‐cause and cause‐specific mortality. Age groups at death were studied at 10‐year intervals. During 662,471 person‐years of follow‐up of 30,943 patients with NAFLD, there were 2097 deaths. The top three causes of death were pneumonia, extrahepatic cancer, and cardiovascular diseases. Liver disease was the sixth leading cause of death in patients aged 70–79 and 80–89 years, accounting for 5.1% and 5.9% of deaths, respectively, but only accounted for 3% or fewer of the deaths in the other age groups. Nonetheless, liver disease was the leading cause of death in patients with NAFLD‐related cirrhosis, accounting for 36.8% of all deaths. The incidence of liver‐related death was higher in men younger than age 70 but higher in women afterwards. The incidence of liver‐related death in women increased from 0.62 to 7.14 per 10,000 person‐years from age 60–69 to 70–79 years. Conclusion: The relative importance of liver‐related death increases with age in patients with NAFLD, especially among women. In patients with cirrhosis, liver disease is the leading cause of death.
CDK4/6 Inhibition Enhances Oncolytic Virus Efficacy by Potentiating Tumor-Selective Cell Killing and T-cell Activation in Refractory Glioblastoma
Authors: Jingshu Xiao, Jiaming Liang, Junjie Fan, Panpan Hou, Xiaodong Li, Haipeng Zhang, Kai Li, Lang Bu, Ping Li, Miao He, Yongheng Zhong, Liping Guo, Penghui Jia, Qiaoqiao Xiao, Junyu Wu, Hong Peng, Chunmei Li, Fan Xing, Deyin Guo
Journal: Cancer Research (2022)

Abstract Glioblastoma (GBM) is among the most aggressive human cancers. Although oncolytic virus (OV) therapy has been proposed as a potential approach to treat GBM, it frequently fails because GBM cells are usually nonpermissive to OV. Here, we describe a dual-step drug screen for identifying chemical enhancers of OV in GBM. From a high-throughput screen of 1416 FDA-approved drugs, an inhibitor of CDK4/6 was identified as the top enhancer, selectively increasing potency of two OV strains, VSVΔ51 and Zika virus. Mechanistically, CDK4/6 inhibition promoted autophagic degradation of MAVS, resulting in impaired antiviral responses and enhanced tumor-selective replication of VSVΔ51 in vitro and in vivo. CDK4/6 inhibition cooperated with VSVΔ51 to induce severe DNA damage stress and amplify oncolysis. In GBM xenograft models, combined treatment with CDK4/6 inhibitor and VSVΔ51 significantly inhibited tumor growth and prolonged the survival of tumor-bearing mice. Further investigation revealed that CDK4/6 inhibitor and VSVΔ51 synergistically induced immunogenic cell death and boosted antitumor immunity. Together, this study features a promising approach of treating aggressive GBM through the combination of CDK4/6 inhibitor with OV. Significance: This study proposes inhibition of cyclin-dependent kinases as a clinically translatable combinatorial strategy to enhance the efficacy of oncolytic virotherapy in GBM.
Common Trajectories of Highly Effective CD19-Specific CAR T Cells Identified by Endogenous T-cell Receptor Lineages
Authors: Taylor L. Wilson, Hyunjin Kim, Ching-Heng Chou, Deanna Langfitt, Robert C. Mettelman, Anastasia A. Minervina, E. Kaitlynn Allen, Jean-Yves Métais, Mikhail V. Pogorelyy, Janice M. Riberdy, M. Paulina Velasquez, Pratibha Kottapalli, Sanchit Trivedi, Scott R. Olsen, Timothy Lockey, Catherine Willis, Michael M. Meagher, Brandon M. Triplett, Aimee C. Talleur, Stephen Gottschalk, Jeremy Chase Crawford, Paul G. Thomas
Journal: Cancer Discovery (2022)

Current chimeric antigen receptor-modified (CAR) T-cell products are evaluated in bulk, without assessing functional heterogeneity. We therefore generated a comprehensive single-cell gene expression and T-cell receptor (TCR) sequencing data set using pre- and postinfusion CD19-CAR T cells from blood and bone marrow samples of pediatric patients with B-cell acute lymphoblastic leukemia. We identified cytotoxic postinfusion cells with identical TCRs to a subset of preinfusion CAR T cells. These effector precursor cells exhibited a unique transcriptional profile compared with other preinfusion cells, corresponding to an unexpected surface phenotype (TIGIT+, CD62Llo, CD27-). Upon stimulation, these cells showed functional superiority and decreased expression of the exhaustion-associated transcription factor TOX. Collectively, these results demonstrate diverse effector potentials within preinfusion CAR T-cell products, which can be exploited for therapeutic applications. Furthermore, we provide an integrative experimental and analytic framework for elucidating the mechanisms underlying effector development in CAR T-cell products.
Mechanisms of ultrasound-microbubble cavitation for inducing the permeability of human skin
Authors: Ai-Ho Liao, Yu-Chen Chen, Chia-Yu Chen, Shun-Cheng Chang, Ho-Chiao Chuang, Dao-Lung Lin, Chien-Ping Chiang, Chih-Hung Wang, Jehng-Kang Wang
Journal: Journal of Controlled Release (2022)
Evolution of drug-eluting coronary stents: a back-and-forth journey from the bench to bedside
Authors: Johny Nicolas, Carlo Andrea Pivato, Mauro Chiarito, Frans Beerkens, Davide Cao, Roxana Mehran
Journal: Cardiovascular Research (2022)

Abstract Coronary stents have revolutionized the treatment of coronary artery disease. Compared with balloon angioplasty, bare-metal stents (BMSs) effectively prevented abrupt vessel closure but were limited by in-stent restenosis (ISR) due to smooth muscle cell proliferation and neointimal hyperplasia. The first-generation drug-eluting stent (DES), with its antiproliferative drug coating, offered substantial advantages over BMSs as it mitigated the risk of ISR. Nonetheless, they had several design limitations that increased the risk of late stent thrombosis. Significant advances in stent design, including thinner struts, enhanced polymers’ formulation, and more potent antiproliferative agents, have led to the introduction of new-generation DES with a superior safety profile. Cardiologists have over 20 different DES types to choose from, each with its unique features and characteristics. This review highlights the evolution of stent design and summarizes the clinical data on the different stent types. We conclude by discussing the clinical implications of stent design in high-risk subsets of patients.
Large-cell transformation is an independent poor prognostic factor in Sézary syndrome: analysis of 117 cases
Authors: Christophe Bontoux, Adèle de Masson, Nicolas Thonnart, Caroline Ram-Wolff, Flavien Caraguel, Luciana Batista, Sabrina Carpentier, Hélène Moins-Teisserenc, Jacqueline Rivet, Marie-Dominique Vignon-Pennamen, Anne Marie-Cardine, Martine Bagot, Maxime Battistella
Journal: British Journal of Dermatology (2022)
Type of Oral Anticoagulant and Adverse Clinical Outcomes in Patients Extending Anticoagulation Therapy Beyond 90 Days After Hospitalization for VTE—Reply
Authors: Katsiaryna Bykov, Joshua J. Gagne
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Tetracycline-induced mitohormesis mediates disease tolerance against influenza
Authors: Adrienne Mottis, Terytty Y. Li, Gaby El Alam, Alexis Rapin, Elena Katsyuba, David Liaskos, Davide D’Amico, Nicola L. Harris, Mark C. Grier, Laurent Mouchiroud, Mark L. Nelson, Johan Auwerx
Journal: Journal of Clinical Investigation (2022)

Mitohormesis defines the increase in fitness mediated by adaptive responses to mild mitochondrial stress. Tetracyclines inhibit not only bacterial but also mitochondrial translation, thus imposing a low level of mitochondrial stress on eukaryotic cells. We demonstrate in cell and germ-free mouse models that tetracyclines induce a mild adaptive mitochondrial stress response (MSR), involving both the ATF4-mediated integrative stress response and type I interferon (IFN) signaling. To overcome the interferences of tetracyclines with the host microbiome, we identify tetracycline derivatives that have minimal antimicrobial activity, yet retain full capacity to induce the MSR, such as the lead compound, 9-tert-butyl doxycycline (9-TB). The MSR induced by doxycycline (Dox) and 9-TB improves survival and disease tolerance against lethal influenza virus (IFV) infection when given preventively. 9-TB, unlike Dox, did not affect the gut microbiome and also showed encouraging results against IFV when given in a therapeutic setting. Tolerance to IFV infection is associated with the induction of genes involved in lung epithelial cell and cilia function, and with downregulation of inflammatory and immune gene sets in lungs, liver, and kidneys. Mitohormesis induced by non-antimicrobial tetracyclines and the ensuing IFN response may dampen excessive inflammation and tissue damage during viral infections, opening innovative therapeutic avenues.